Haiti: Cholera Mutations Could Lead to Severe Disease

The cholera strain that transferred to Haiti in 2010 has multiple toxin gene mutations that may account for the severity of disease and is evolving to be more like a 1800s version of cholera, reports a new Northwestern University study.

The strain, "altered El Tor," which emerged around 2000, is known to be more virulent and to cause more severe diarrhea and dehydration than earlier strains that had been circulating since the 1960s. This study reports the altered El Tor strain has acquired two additional signature mutations during the past decade that may further increase virulence.

In addition, these newly discovered signature mutations documented in the study further link the Haitian cholera epidemic to the strain from Nepal.

The study suggests the strain with multi-signature toxin gene mutations may trigger a unique pattern of infection accounting for the severity of disease noted during the Haiti cholera outbreak.
"The cholera strain from the 1800s epidemic did the same thing," said Karla Satchell, the senior author of the study. "That strain also modified its toxin genes and the cholera got worse."

Satchell and colleagues analyzed publicly available genomic sequencing data and found this new cholera strain had accumulated some curious genetic changes during its global spread. First, the main cholera toxin that causes the diarrhea acquired genetic changes that converted the toxin to a form similar to that produced by strains prevalent during the historic cholera epidemics of the 1800s.

Surprisingly, this new strain next acquired a genetic lesion that inactivated the MARTX toxin, previously recognized to be important for evading the immune system. A third as yet uncharacterized genetic mutation in the cholera toxin followed, suggesting a mutation emerged in the cholera toxin to compensate for the loss of MARTX.

These mutations occurring in the same strain indicate that the bacterium interacts differently with the immune system than previous strains.

"Perhaps this results in the bacterium more successfully evading early detection after a person accidently drinks cholera infected fluids," Satchell said. "Interestingly, these multiple mutations in important proteins that specifically contribute to disease could explain why this strain is causing more severe disease, although the contribution of each mutation to human infection remains to be studied."